It is not as yet possible to describe in specific terms the well-known increase in the yellow color and visible non-tryptophan fluorescence which occurs with aging of the human lens and with the appearance and progress of certain types of senile cataract. This is specially evident regarding the molecular basis of those modifications. Our knowledge of the molecular species being accumulated in the aging and cataract lens is rather incomplete. A systematic analytical comparative study of individual normal and cataract human lenses will be undertaken as the first step in the accomplishment of our goal, i.e., the isolation and molecular characterization of the yellow-fluorescent species in cataract lenses (more available than normal lenses). We have selected as the basis fOr this study the endopeptidase-resistant fraction that can be obtained from single lenses by sequential proteolysis and chromatography of the digests, because the peptides in this fraction represent the most modified protein region of the lens, regarding yellowing and unusual flouorescence. Components in this fraction will be resolved by ion-exchange chromatography and the peptide profiles from normal lenses of differing age and cataract lenses of various characteristics will be compared. Further fragmentation of the most relevant peptides in the endopeptidase-resistant fraction and separation of the resulting fragments will allow additional comparisons to be made at a level closely reflecting the properties of the underlying colored or fluorescent components. As the result of the information provided by these analytical studies we expect to define small peptide fragments representative of the color and fluorescence of the lens and obtainable from pools of cataract lenses in sufficient amounts to be structurally analyzed by conventional physico-chemical methods.